this study combines data from 3 other studies testing empagliflozin in patients with diabetes or with chronic heart failure. the study looks at the numbers of patients who had lower limb amputations

Conditions: Diabetes Mellitus, Type 2

Summary: the primary objective of this exploratory meta-analysis is to evaluate the frequencies, incidence rates, and hazard ratios of lower-limb amputation (lla) events (primary outcome) and of adverse events related to amputation (secondary outcome) in patients treated with empagliflozin compared with placebo in the pooled population of the long-term studies 1245.25, 1245.110, and 1245.121 (saf-m1), in the pooled population of studies 1245.110 and 1245.121 (safm2), and in each of the 3 studies separately.


Eligibility criteria:
inclusion criteria for 1245.25: * age ≥18 years, diagnosis of type 2 diabetes mellitus (t2dm) * drug-naïve or pretreated with any background therapy * glycated haemoglobin (hba1c) criteria * patients who were drug-naïve: hba1c of 7 to 10% * patients with background therapy: hba1c of 7 to 9% * body mass index (bmi) ≤45 kg/m2 * with high cardiovascular risk, defined as ≥1 of the following criteria * history of myocardial infarction (\>2 months prior to enrollment) * multi-vessel coronary artery disease: ≥2 major vessels or left main coronary artery * single-vessel coronary artery disease with no scheduled revascularization/previously unsuccessful revascularization * hospital discharge due to unstable angina pectoris (\>2 months prior to enrollment) * history of stroke (\>2 months prior to enrollment) * peripheral occlusive arterial disease inclusion criteria for 1245.110 and 1245.121 * age ≥18 years (japan, age ≥20 years) * chronic heart failure (hf) new york hear association (nyha) class ii to iv * ejection fraction (ef) and n-terminal of the prohormone brain natriuretic peptide (nt-probnp) criteria * 1245.110: preserved ef (left ventricular ejection fraction (lvef) \>40%) and elevated nt-probnp (\>300 pg/ml; \>900 pg/ml for patients with atrial fibrillation) * 1245.121: reduced ef (lvef ≤40%) and elevated nt-probnp (≥2500 pg/ml if ef 36 to 40%, ≥1000 pg/ml if ef 31 to 35%, ≥600 pg/ml if ef ≤30% or if ef ≤40% with documented hospitalisation for hf within 12 months prior to screening; for patients with atrial fibrillation, double the level of nt-probnp is applied for each ef category) * 1245.110 only: structural heart disease within 6 months or documented hospitalisation for hf within 12 months prior to screening * 1245.121 only: stable dose of medical therapy for hf consistent with local and international cardiology guidelines exclusion criteria for 1245.25 * uncontrolled hyperglycemia: fasting plasma glucose \>240 mg/dl * severe renal impairment defined as egfr \<30 ml/min by modification of diet in renal disease (mdrd) formula * intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial, or participating in another trial (involving an investigational drug and/or follow-up) exclusion criteria for 1245.110 and 1245.121 * myocardial infarction, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or transient ischaemic attack ≤90 days before screening * heart transplant recipient, or listed for heart transplant * acute decompensated hf * systolic blood pressure (sbp) ≥180 mmhg at randomisation * symptomatic hypotension and/or sbp \<100 mmhg at screening or randomisation * impaired renal function defined as estimated glomerular filtration rate (egfr) chronic kidney disease epidemiology collaboration equation (based on serum creatinine value) \<20 ml/min/1.73 m2 or requiring dialysis at screening